Inosine-5′-monophosphate dehydrogenase type II (IMPDH2)

Inosine-5′-monophosphate dehydrogenase type II (IMPDH2) is a key rate-limiting enzyme in de novo guanine nucleotide synthesis, catalyzing the NAD-dependent oxidation of inosine-5′-monophosphate to xanthosine-5′-monophosphate, which is then converted to guanosine nucleotides required for DNA and RNA synthesis[1][3]. IMPDH2 is highly expressed in proliferating cells, especially lymphocytes, making it a major target for immunosuppressive and antineoplastic therapies[3][6]. Mycophenolate mofetil is a prodrug that delivers its active metabolite, mycophenolic acid, which acts as a potent, reversible, non-competitive inhibitor of IMPDH2, selectively suppressing T and B cell proliferation and immune responses by limiting guanosine nucleotide availability[4][6][8]. IMPDH2 is upregulated in some cancers, suggesting a potential role in oncogenesis[1].

Other names

IMP dehydrogenase 2IMPDH IIIMPDH2

Competitive, reversible inhibition of de novo guanine nucleotide biosynthesis via IMPDH2, suppressing proliferation of T and B lymphocytes and reducing immune-mediated tissue damage[2][4][6].